This project involves development of a low-power, compact and portable, reliable, safe, and easy-to- operate x-ray diffraction instrument for measurement of crystal concentration and phase composition for active pharmaceutical ingredients (API) in the stages of research, development, and production for the pharmaceutical industry and possibly extended to other industries. This could also be used online for primary measurement of drug quality in pilot production and manufacturing environments. The team of X-ray Optical Systems (XOS), a world leader in manufacturing advanced x-ray optics and optics enabled analyzers, and Bristol-Meyers-Squibb (BMS), a world leader in pharmaceutical research and development, has the expertise necessary to develop a successful instrument. The objective of this SBIR Phase I proposal is to demonstrate the feasibility of developing a compact analyzer capable of monitoring active pharmaceutical ingredients (API) online or at-line in the various stages of development and production. This will be accomplished by developing a novel, low-power, fully enclosed and shielded, parallel-beam x-ray diffraction (XRD) system to apply new analysis techniques. Specifically the powder XRD (PXRD) setup would use a 50 W x-ray Source coupled with a collimating polycapillary x-ray optic to determine the proper crystalline information and polymorphs in the API with a high degree of accuracy. This new technique will be non-destructive, rapid, and insensitive to sample position and roughness. In addition, the system equipment will be compact and portable, therefore, it will be easily integrated in an on-line production system. In order to demonstrate the applicability of this technique, XOS proposes to explore specific API's from the pharmaceutical industry that have been challenging to develop production models for, using existing PXRD technology. Parallel beam XRD has been used for characterization of pharmaceuticals (Yin 2007). This study has already demonstrated the feasibility on a standard laboratory system. Due to the extended footprint, power requirements and chilled-water cooling for high power x-ray source, the system is not suitable for a typical production environment. XOS can leverage the new source-optic coupled technologies to demonstrate the low- power, compact, easy-to-use, measurement method. In Phase I, XOS proposes to develop and demonstrate the performance of the PXRD setup via: 1) differentiation of particular sample characteristics, 2) correlation of new data with conventional laboratory data, 3) reproducibility, and 4) design a novel sample handling method. The proposed analyzer will have a positive impact to the general public by increasing drug development efficiency and shortening the turnaround times for manufacturing processes. The applicability for such a machine includes facilitating improved throughput of drug research with a more rapid and cost effective instrument, implementation of drug process analytical technology (PAT) using a primary measurement method, and improvements in drug quality by design (QbD). [unreadable] [unreadable] [unreadable]